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Wei Zhang, Jin-Da Wang, Ying An, Jing-Shang Zhang, Wei Wang, Shi-Jiang Lu, Robert Lanza, Liang Xu; Human Embryonic Stem Cell-derived Hemangioblasts Can Repair Acute Retinal Vascular Damage. Invest. Ophthalmol. Vis. Sci. 2012;53(14):307.
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© ARVO (1962-2015); The Authors (2016-present)
It was showed that transplanted human embryonic stem cell-derived hemangioblasts localized to injured retinal vasculature in diabetic rats and retinal ischemia-reperfusion injured mice. The study was to verify that the hemangioblasts-derived neovasculature was healthy but not leaky in diabetic rats. Using mice model of oxygen-induced retinopathy (OIR), this study was to investigate the potential of hES-hemangioblasts to rebuild functional vasculature on retina obliteration region and to suppress pre-retinal neovascular tufts.
OIR model was induced using C57BL/6 neonatal mice as described. GFP-labeled hES-derived hemangioblasts were injected intravitreally. At P17, retinas were whole mounted and vascular architectures were visualized by GS-lectin staining or FITC-dextran cardiac perfusion. The area of central vascular obliteration and pre-laminar neovascular tufts were quantified. STZ-induced diabetic rats were given hES-derived hemangioblasts intravitreally 6 weeks after induction. Blood-retina-barrier (BRB) function was evaluated by measuring the concentration of FITC-dextran in retina homogenate. Human CD31 protein expression in retinas was detected by immunofluorescence staining. The contralateral eye of the same animal was injected with the same amount of hES-derived endothelial cells or with the same volume of vehicle alone as control.
In diabetic rats, GFP-positive hemangioblasts incorporated into retinal vessels two days after cell transplantation. The injection of hES-derived hemangioblasts prevented BRB breakdown in diabetic rats. In OIR mice, only hES-derived hemangioblasts but not endothelial cells integrated into retinal vasculature, promoting the process of vascular re-growth and hindering the abnormal formation of neovascular tufts. The areas of both vascular obliteration and neovascular tufts in hemangioblasts-treated eyes were significantly lower than those in control eyes. In both OIR and diabetic models, integrated GFP-positive cells expressed human CD31, indicating the differentiation of hemangioblasts to endothelial cells.
Our study showed that hES-derived hemangioblasts had the ability to form new, functional vasculature network; and repaired vascular inhibited the growth of pathological neovasculature.
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